The present invention relates to certain hydroxylated derivatives of compounds known to be useful as inhibitors of cholesterol biosynthesis.
U.S. Pat. No. 4,681,893, which is incorporated herein by reference, discloses compounds which include trans (.+-.)-5-(4-fluorophenyl)-2-(1-methylethyl)-N, 4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrol e-3-carboxamides, and the corresponding ring-opened acids derived therefrom, and pharmaceutically acceptable salts thereof. One compound from within the group has been found particularly active in inhibiting the biosynthesis of cholesterol, and is thus especially useful in treating atherosclerosis. Specifically, U.S. Pat. No. 5,273,995, which is incorporated herein by reference, describes the optically pure compound, [R-(R*,R*)]-2-(4-fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1-methylethyl)- 3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, pharmaceutically acceptable salts thereof, and the corresponding cyclized lactone form, as being particularly active as a hypocholesterolemic agent. We have now discovered that these compounds are metabolized in vivo to certain phenyl hydroxy derivatives, and that such phenyl hydroxy derivatives are also active as inhibitors of the biosynthesis of cholesterol, and thus can be administered directly to mammals for treating conditions of hypercholesterolemia. An object of this invention therefore is to provide new chemical entities, formulations containing the same, and a method for treating subjects suffering from hypercholesterolemia by administering directly a [(hydroxyphenylamino)carbonyl]pyrrole.